Experiments utilizing myelinated CNS and PNS cultures and parallel animal models are presented which will attempt to dissect certain possible etiologic and pathogenetic mechanisms operative in the inflammatory demyelinating diseases (e.g. multiple sclerosis - MS) and certain CNS diseases linked to chronic infection by myxoviruses e.g. subacute sclerosing panencephalitis - SSPE. Evidence of autosensitization to CNS components (e.g. myelin) and/or viral antigen in these diseases are major objectives of this proposal. In addition, the behavior of known defective SSPE virus strains (both cell-free and cell-associated) will be observed by a variety of morphologic techniques in CNS cultures to sera and lymphocytes from Strain 13 guinea pigs suffering from a form of chronic EAE which has been recently studied in this laboratory. This disease is usually progressive and has both clinical and morphologic similarities to MS. Sera and lymphocytes will be taken at different stages of the chronic disease and attempts will be made to correlate their demyelinating activity in CNS cultures with the clinical and pathologic stage of the disease to see whether the in vitro test has diagnostic potential. Utilizing IgG conjugated to horseradish peroxidase (HRP), the site of action of the demyelinating factors will be sought by EM. The specificity of oligodendrocytes to degenerate in the demyelinating diseases will be studied with CNS tissue and sera from animals sensitized with purified preparations of bulk isolated oligodendrocytes. The effect of these sera upon oligodendroglia will be tested in ability to bind to normal and abnormal oligodendroglia in vitro. Oligodendroglia in acute MS plaques will also be studied using this anti-oligodendroglial cell IgG-conjugate. Other experiments will attempt by immunocytologic techniques to locate viral antigens in MS plaques and whether there is any specificity for MS serum or CSF IgG to bind to MS lesions. Experiments on SSPE virus-infected cultures will attempt to define how cell-associated SSPE virus spreads from cell to cell. Finally acute MS lesions will be subjected to freeze-fracture technology to look for cell surface aberrations.